5-Hydroxytryptamine2BReceptor Mediates Contraction in the Mesenteric Artery of Mineralocorticoid Hypertensive Rats

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Abstract
Vascular responsiveness to 5-hydroxytryptamine (5-HT) is dramatically increased in hypertension. The hypothesis that augmented vasoconstriction to 5-HT in hypertension is due to a change in receptor subtype on vascular myocytes was tested. Mesenteric arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive (systolic blood pressure >180 mm Hg) and sham normotensive (systolic blood pressure tryptamine>5-hydroxykynuramine). 5-HT was approximately 10-fold more potent in contracting mesenteric arteries from DOCA-salt hypertensive rats compared with arteries from sham normotensive rats. The tryptophan metabolite kynuramine, which possesses significant contractile activity at the 5-HT2Breceptor, contracted hypertensive arteries significantly (50% of 5-HT maximum) but not sham arteries. Ketanserin (5-HT2Aantagonist) competitively inhibited contraction to 5-HT in arteries from normotensive rats (−log dissociation constant [mol/L]; pKB=8.54) but not from hypertensive rats (pKB>6.5). Moreover, contraction to kynuramine was not blocked by ketanserin. Thus, under normal conditions, 5-HT2Areceptors mediate contraction to 5-HT. However, in DOCA-salt hypertension, ketanserin-insensitive 5-HT2receptors, possibly 5-HT2Breceptors, mediate mesenteric arterial contraction to 5-HT.